Impaired fibrinolysis and early atherosclerosis in impaired glucose tolerance and newly detected type 2 diabetes

Impaired fibrinolysis has been suggested to contribute to excessive atherosclerosis in diabetes. However, the role of defective fibrinolysis in the early stages of atherosclerosis in the prediabetic phase remains unclear. Since the intima-media thickness (IMT) of the common carotid artery is a good indicator of early atherosclerosis, we examined the relationship of fibrinolytic parameters - plasminogen activator inhibitor-1 (PAI-1) antigen (active and total) and tissue-type plasminogen activator (tPA) antigen with atherosclerosis risk factors and carotid IMT in various degrees of glucose intolerance. 424 middle-aged subjects were examined - 249 with normal glucose tolerance (NGT), 107 with impaired glucose tolerance (IGT) and 68 with newly diagnosed diabetes mellitus (NDM). IMT of the common carotid artery was examined by B-mode of ultrasound. Fibrinolytic parameters (PAI-1 antigen and tPA antigen) and plasma lipoproteins - triglycerides, total and HDL cholesterol were measured by conventional methods; real insulin and proinsulin by highly specific enzyme immunoassays. The diabetic individuals showed significantly higher PAI-1 antigen in comparison to the NGT and IGT group. TPA antigen was significantly higher in the NDM group, however, this difference disappeared after age and sex adjustment. PAI-1 (total and active) and tPA antigen raised in quintiles for fasting plasma glucose below the cut-off limits for diabetes. IMT increased in quintiles for PAI-1 active antigen with a significant difference between the Ist and the 5th quintiles, However, this difference was no longer statisically significant after adjustment for age and sex. PAl-1 and tPA antigen were significantly positively correlated with atherosclerosis risk factors: body mass index, waist to hip ratio, fasting and postprandial plasma glucose, HbA1c, real insulin, proinsulin, triglycerides, total cholesterol and inversely to HDL cholesterol. In addition PAI-1 and tPA antigen correlated significantly to carotid IMT. In conclusion: we observed impaired fibrinolysis already in prediabetic subjects. PAl-1 and tPA antigen correlate to the established components of the metabolic syndrome and to carotid IMT.